The objectives for the second year of support are to investigate further: (1)\the significance of endogenous circulating acid-labile alpha interferon (IFN) in AIDS patients, particularly in homosexual men with AIDS who receive antineoplastic therapy with alpha IFN; and (2)\the basis for deficient biochemical responsiveness to IFN in peripheral blood mononuclear cells (PBMC) from patients with AIDS. To do this, we will: (1)\continue prospective follow-up of several cohorts of homosexual men; (2)\test for circulating IFN and IFN-induced enzymes in homosexual patients with AIDS who receive therapy with recombinant alpha IFN at the NIH Clinical Center; (3)\test the effects of IFN on established Kaposi's sarcoma (KS) cell lines in vitro; and (4)\investigate several factors, such as soluble inhibitors and virus infection that might affect expression of IFN-induced enzymes. Circulating IFN will be assayed and characterized before IFN therapy begins and at various times during dose-escalation therapy with purified recombinant alpha IFN. PBMC will also be isolated, and cytoplasmic extracts prepared for measurement of two independent IFN-induced enzymes, 2'-5' oligoadenylate (2-5A) synthetase and protein kinase (PK). PBMC from only 10 of 28 AIDS patients tested so far developed increased 2-5A synthetase following exposure to IFN in vitro or during therapy with human lymphoblastoid IFN. Measurement of PK will help to determine whether this is due to a specific block in 2-5A synthetase or to a general inability of the PBMC to respond to IFN. Aliquots of the 2-5A synthetase reaction product will also be analyzed by HPLC to determine if the enzyme has been induced but makes nonfunctional 2-5A dimers that are not detected by our usual assay procedure. Results will be correlated with the clinical outcome of therapy and with virologic and immunologic data on the patients. KS cell lines treated with human alpha or gamma IFN will be tested for antiviral state, 2-5A synthetase, and PK and sensitivity to NK cell killing. These results will be compared with the levels of 2-5A synthetase and PK in KS biopsy tissue obtained from patients before and during alpha IFN therapy. We will also determine if circulating factors that are present in most homosexual men, such as immune complexes and antibody to asialo GM1, or infection with EBV, CMV or HTLV I, II, or III, inhibit the ability of PBMC from normal persons to respond to IFN with increased levels of IFN-induced enzymes. (IS)